Matlock, William;
Rodger, Gillian;
Pritchard, Emma;
Colpus, Matthew;
Kapel, Natalia;
Barrett, Lucinda;
Morgan, Marcus;
... Stoesser, Nicole; + view all
(2025)
Escherichia coli phylogeny drives co-amoxiclav resistance through variable expression of TEM-1 beta-lactamase.
Nature Communications
, 16
, Article 8669. 10.1038/s41467-025-63714-6.
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Abstract
Co-amoxiclav (amoxicillin and clavulanate) is a commonly used combination antibiotic, with resistance in Escherichia coli associated with increased mortality. The class A beta-lactamase blaTEM-1 is often carried by resistant E. coli but exhibits high phenotypic heterogeneity, complicating genotype-phenotype predictions. We curated a dataset of n = 377 diverse E. coli isolates where the only acquired beta-lactamase was blaTEM-1. We generated hybrid assemblies and co-amoxiclav minimum inhibitory concentrations (MICs), and blaTEM-1 qPCR expression data for a subset (n = 67/377). We first tested whether intrinsic expression of blaTEM-1 varied between E. coli lineages, for example, from regulatory system differences, which are challenging to genomically quantify. Using genotypic features, we built a hierarchical Bayesian model for blaTEM-1 expression, controlling for phylogeny. Expression varied across the phylogeny, with some lineages (phylogroups B1 and C, ST12) expressing blaTEM-1 more than others (phylogroups E and F, ST372). Next, we built a second model to predict isolate MIC from genotypic features, again controlling for phylogeny. Phylogeny alone shifted MIC past the clinical breakpoint in 19% (55/292) of isolates with greater-than-chance probability, mostly representing ST12, ST69 and ST127. A third causal model confirmed that phylogenetic influence on blaTEM-1 expression drove variation in MIC. We speculate that intergenic variation underlies this effect.
| Type: | Article |
|---|---|
| Title: | Escherichia coli phylogeny drives co-amoxiclav resistance through variable expression of TEM-1 beta-lactamase |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-025-63714-6 |
| Publisher version: | https://doi.org/10.1038/s41467-025-63714-6 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212884 |
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